Attempts have been made in recent years to apply various drugs to intrabuccally quick disintegrating tablets, but drugs having bitter tastes are limited to only drugs having weak bitterness. Thus, virtually nothing is known about bitterness-reducing techniques which can be generally used for various drugs having bitter tastes, do not spoil characteristics of intrabuccally quick disintegrating tablets and also do not reduce bioavailability.
Bitter drugs are present in many numbers, but when their application to pharmaceutical preparations is considered, it is general to select a method in response to the degree of bitterness of each drug. Illustratively, some methods such as a method in which an additive such as a flavor or a sweetener is added and a film coating method which uses a polymer base are known. According to the method in which a flavor or a sweetener is added, it is difficult to mask bitter tastes by the method alone so that it can be applied to only limited drugs.
Also, the generally known film coating method which uses a polymer base is selected mostly for the purpose of controlling release of drugs. Thus, the significance for selecting this method in reducing bitter tastes of bitter drugs is to control release of a drug in the mouth to a threshold value or less of the drug. The term threshold value as used herein means a limit of drug concentration by which its bitterness is felt, so that the bitterness is not felt when its concentration is lower than this level. Also, in general, a drug having a high threshold value, namely a drug having a high limit concentration by which a bitter taste is felt, can be said that the degree of bitterness is “weak”, and a drug having low threshold value can be said that the degree of bitterness is “strong” on the contrary.
However, when a pharmaceutical preparation is obtained by applying the film coating method to a drug having low threshold value, particularly when a pharmaceutical preparation is made into a dosage form such as intrabuccally quick disintegrating tablets which do not accompany taking of water, it is necessary to control amount of the drug to be released in the mouth as small as possible by increasing the coating amount, thus causing a problem as a result that sufficient release of the drug in the digestive tract cannot be secured and bioavailability is reduced in comparison with conventional pharmaceutical preparations.
In addition to these methods, JP-A-6-284866 (corresponds to U.S. Pat. No. 5,785,984) regarding a taste improving agent discloses a protein-lipid complex and JP-A-8-9897 regarding a coating composition of a bitterness-containing substance discloses an acidic phospholipid or its lysate thereof. These inventions take note of the bitterness receiving mechanism carried out by gustatory organ in the mouth and the interaction between a bitter drug and a lipid and describe that these substances are effective in reducing bitter tastes. However, since these substances contain phospholipids, they are unstable to temperature and heat and have a possibility of reducing stability during production or storage of the pharmaceutical preparations, so that their materialization has a difficulty.
Accordingly, the object of the present invention is to provide a method for reducing bitterness of bitter drugs, which does not cause delay of release rate, does not show reduction of bioavailability in comparison with conventional pharmaceutical preparations and, due to the use of additives generally used in the field of pharmaceutical preparation, has high practical value, can be applied to various drugs and does not spoil characteristics of intrabuccally quick disintegrating tablets, and intrabuccally quick disintegrating tablets in which bitter tastes are reduced.